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Highlights of Chapters 1

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Title: Highlights of Chapters 1


1
Highlights of Chapters 12
  • Key discoveries and Theories
  • Three Kingdoms
  • Cell and Genomes
  • Cell Chemistry

2
Fundamental questions
  • What is the origin of life
  • How does life propagate
  • How can a single cell form a complex organism
  • 1859 Charles Darwin, Alfred Wallace
  • Evolution origin of species - natural selection
    fittest selected by forces of their environment
  • biological adaptation
  • Genes of different species are closely related
  • For instance some human genes will function in
    yeast and fly

3
Historical perspective of cell biology
  • 1950-1960 Golden age for cell/molecular biology
  • Fundamental breakthroughs basis for todays
    molecular understanding of biological systems
  • Structure of DNA (stores genetic information,
    heredity)
  • Central dogma (DNA RNA
    Protein)
  • Genetic code (universal)
  • Gene regulation (when, what and how much)
  • 1980-Present Information age of molecular
    biology

4
MOLECULES OF LIFE
Water most abundant 75-80 by wt inorganic
ions, small organic molecules such as sugars,
vitamins and fatty acids can be made or
imported Macromolecules protein, DNA, RNA,
polysaccharides must synthesize these Proteins
and DNA are polymers of monomeric units amino
acids for proteins (20) nucleic acids for DNA
(4) proteins are the workhorses (proteins are
versatile) (enzymatic activity, structural
proteins, transport) DNA is the master
molecule
5
Genetic analysis(Inheritance of characteristics)
  • 1865 Gregor Mendel Pea plant
  • Important characteristics of his expts
  • Pollination control easy
  • Pure strains
  • Defined characteristics
  • Large sample size

6
1865 Breeding Experiments with Yellow Green Pea
seeds
X
F1
X
F2
  • Dominant/recessive
  • 2 hereditary units (genes)
  • Independent assortment (linked traits)
  • One gene copy Allele

7
  • 1953 Modern Era of Molecular Biology
  • Watson/Crick, Structure of DNA
  • double helix
  • Chargoffs rules, GC TA,
  • rules underlying the base pairing
  • Wilkin/Franklin X-ray diffraction pattern
  • helical nature, diameter, distance bet
    adjacent bp
  • RNA, genetic code
  • 1959 Crystal structure of protein
  • Structure function relationships
  • Cell structure Electron microscope, cell
    culture

8
1961 - Jacob and Monod Regulation of gene
1950 - 60 - establishment of cell culture
Protein sequencing 1970 identification of
specific restriction enzymes dawn of cut
and paste molecular genetics advent of
rapid DNA sequencing oligonucleotide
(DNA) synthesis 1980 Polymerase chain
reaction 1990 Genome sequencing
Functional genomics Systems analysis
Proteomics
9
Three animal Kingdoms
Eukarya
Bacteria
Archaea
Common single cell progenitor
Based on DNA sequence similarity Archaea are
more related to humans than bacteria.
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Prokaryotes
  • Prokaryotes
  • DNA is not sequestered
  • Simple internal organization

12
Eukaryotes
  • Eukaryotes
  • Have a nucleus compartment for DNA
  • organelles

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Cells are small
15
Proteins are even smaller
Cell volume 3.4 X 10-9 ml
Weighs 3.5 X 10-9 grams
20 protein 7 X 10-10 grams
Average protein size 52,700 grams/mol
7.9 X 109 proteins/cell
10,000 different proteins in cell
Suggests that there are over a million copies of
each protein. However, levels of certain proteins
are tightly controlled. Insulin receptor 20,000
copies per cell actin 5 X 108 copies
Many proteins within the cell are enzymes
16
Problem How do cells keep inside water in and
keep outside water out?
All cells are surrounded in a lipid membrane
What other function can membranes serve?
17
Organelles
Mitrocondria-power plants
Endoplasmic reticulum-place to make membrane
proteins and secreted proteins and lipids
Golgi vessicles-further refine membrane
proteins and direct their transport to specific
surfaces of the cell
Peroxisomes-remove fatty acids, hydrogen
peroxide and amino acids
Lysosomes-degrade old proteins and foreign
materials
18
The Superstructure of the Cell
Blue DNA Red actin cytoskeleton Green tubulin
cytoskeleton
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DNA
4 nucleotides based-paired GC, AT. Watson and
Crick solved structure. DNA strand coiled
around a common axis forming a double helix
21
Flow of genetic information
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Advent of genetic organization Chromosomes
resides in the nucleus means by which genetic
information is transferred number and size are
constant in an organism each chromosome
single DNA molecule (plus proteins) can be
considered a string of genes total DNA
genome visible during cell division Somatic
cells diploid (2n), homologous pairs (mitosis)
Germ cells haploid (n) only one of each pair
(meiosis) fruit fly (Drosophila) 4 corn
10 peas 7 humans 23
25
Chromosome
One human cell has 2 m of DNA found in 46
chromosomes packed into a 0.006 mm3 nucleus
26
Chemical nature of the gene Arranged as regular
linear arrays Gene order could change Gene
activity Biochemical activity One
gene - One protein DNA contains all
information subject to variation/random
change faithful reproduction (like begets
like) underlies development of every new
organism
S
R
S
27
LIFE CYCLE OF CELLS
  • Steady state system in adult organism
  • balanced system (no net growth)
  • DNA Proteins (maintenance)
  • DNA replication
  • Cell division
  • Cell differentiation
  • Cell apoptosis

Normal cell turnover RBC nerve cells
reproductive tissues
28
The Cell cycle
M mitosis G1 first gap S - synthesis G2
second gap G0 growth arrest checkpoints
Cell Cycle follows a regular timing
mechanism Eukaryotes Prokaryotes have no
G0 Cell division 10-20 hrs vs 20-30 min
29
Mitosis
Mitosis Partitions genome equally at cell
division Prophase, metaphase, anaphase,
telophase Cytokinesis, mitotic apparatus
30
Mitosis
31
(go to movies)
32
Meiosis
33
  • Cell Death/Apoptosis/Programmed cell
    death/Anoikis
  • Balances cell growth multiplication
  • eliminates unnecessary cells
  • (development, restructuring, damaged cells)
  • internal program (clock)
  • follows systematic events (DNA frag, membran
  • blebbing, consumed by macrophages)
  • Now an important area of cancer research

34
  • Cells are organized into Tissues
  • Extracellular matrix (ECM)
  • network of proteins and polysaccharides
  • Cell-adhesion molecules
  • cell-cell contact
  • cell-ECM contact
  • basal lamina
  • endothelium

35
  • Body Patterning dictated by patterning genes
  • program of genes specify the body plan
  • local interactions induce specific program
  • Conserved throughout evolution
  • axial symmetry
  • integration / coordination of multiple events
    during
  • embryogenesis
  • 1 2 3
  • genetic program cell contact soluble
    factors
  • gene expression adhesion signaling

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Heart Development Requires Proper Vessel Growth
and Differntiation of many different cell types
38
CHAPTER 2 Cell Chemistry and Biosynthesis
Chemical concepts underlying cellular
processes Basic principles of chemistry and
physics direct biological processes. No
supernatural force is required for biological
processes BONDS and STABILIZING FORCES CHEMICAL
EQUILIBRIUM ENERGY CENTRAL ROLE OF ATP ENZYMES
39
WATER constitutes 70-80 small molecules
7 Rest - MACROMOLECULES BUILDING BLOCKS Amino
acids Proteins Nucleotides DNA and
RNA Sugars Complex Carbohydrates
40
CHEMICAL BONDS Covalent (50-200) Noncovalent
(1-5 kcal/mole) - Strong - Weak - sharing
electrons - 3D structure within atoms of an
- inter and intra molecular individual
molecule - Strength cooperation - multiple,
weak bonds - transient, dynamic
Orbitals
Nucleus protons
Electrons
41
  • Covalent Bonds
  • A. Atoms in biological systems
  • Hold the atoms within a molecule
  • Formed by sharing electrons in the outer atomic
    orbitals
  • Forms the basis of chemical reactivity and basic
    shape
  • H C N P O S
  • 1 4 3
    5 2 2,6
  • Each atom can make a defined of covalent bonds
  • Depends on the number of electron in the
    outermost
  • orbital and their size

42
  • typically stable (making/breaking bonds requires
    energy)
  • energy required to break a single bond (50-100
    kcal/mol)
  • double bond (120-170 kcal/mol) triple (195 )
  • Examples
  • - phosphorous biologically very important
  • - esters of sulfuric acid proteoglycans in
    ECM
  • B. Bonds are oriented at precise angles (shape)
  • 104.5 (water, each
    single bond)
  • dependent upon mutual repulsion of outer e
    orbitals
  • non-bonding electrons also contribute to
    properties/shape
  • double bond are more rigid (cannot rotate
    freely)

H
O
H
43
  • D. Asymmetric carbon (common in biological
    molecules)
  • a carbon atom bonded to four dissimilar atoms
  • COOH COOH
  • H - C - NH2 NH2 - C - H
  • CH3
    CH3
  • mirror image
  • Optical isomers (stereoisomers) designated D or
    L
  • Central C is called chiral carbon (alpha C)
  • All naturally occurring aa in proteins are L.
  • only D form of sugars (carbohydrates are found)
  • different biological activity, but identical
    chemical property

D-alanine
L-alanine
44
  • NON COVALENT BONDS or INTERACTIONS
  • Hydrogen bond
  • Ionic Interactions
  • van der Waals Interactions
  • Hydrophobic bond
  • Important for stabilizing 3D structures
  • Inter- and Intra-molecular
  • Multiple bonds give strength
  • Transient/dynamic

45
  • Hydrogen Bond ( 5 kcal/mol)
  • Underlies chemical and biological property of
    water
  • When H atom covalently bonded to another atom
    (donor,D)
  • forms a weak association (the hydrogen
    bond) with an
  • acceptor (A) atom
  • Both D, A electronegative and polar
  • Most D, A are N (3.0) or O (3.4)
  • N-H C-H
  • O-H
  • Forms the basis of solubility (hydrophilic
    water loving)
  • More H bonds, more soluble
  • Standard length (0.26-0.31 nm) and directionality
    (linear/strong)
  • Stabilizing force is multiplicity
  • H bonding usually involves exclusion of a H2O
    molecule

polar
nonpolar
46
  • B. IONIC INTERACTIONS
  • When bonded atoms have very different
    electronegativilty
  • e- found among more electronegative atom
    (NaCl-)
  • no fixed orientation/angel
  • vely charged ion (Cation) _vely charged
    (Anion)
  • Na, K, Ca2, Mg2, Cl-
  • typically exist complexed to H2O (using the
    water dipole)
  • important biological roles (nerve impulses,
    muscle contraction)
  • very soluble and energy is released as they bind
    water
  • energy of hydration

47
  • C. Van der Waals Interactions ( 1kcal/mol)
  • non-specific attractive force is created as two
  • atoms approach each other closely
  • transient / momentary fluctuations in the
    distribution of e
  • generating a transient electric dipole
  • seen in all types of molecules (polar and
    non-polar)
  • H bonds, ionic interactions can override VDW
  • Van der Waal radii balance attraction
    repulsion
  • antigenantibody / enzymesubstrate
  • facilitated by their complementary shape

48
  • D. HYDROPHOBIC BONDING (force that causes
    hydrophobic
  • molecules to aggregate rather than dissolve)
  • non-polar molecules (for example hydrocarbons)
  • no ions, no dipole moment, no hydration
  • Force that causes non-polar molecules to
    aggregate
  • Basic force for BIOMEMBRANE structure
  • A phospholipid bilayer typically separates two
    aqueous
  • compartments (plasma membrane and organelle
    memb)
  • Phospholipids are amphipathic (tolerant of both)
    molecules

Fatty acyl chains glycerol phosphate
alcohol Hydrophobic Hydrophilic
49
Orient their hydrophilic ends to The aqueous
environment
Spontaneously organize into structures (micelle,
liposomes, bilayer) Impermeable to salt, sugar
and small molecules VdW interactions stabilize
the close packing This structure is very
fluid Proteins span the phospholipid bilayer
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  • CHEMICAL REACTIONS
  • covalent bonds are broken and re-formed
  • several hundred different rxns may occur
    simultaneously
  • in a given cell
  • what rxns can proceed (rate/extent) depend on
    multiple
  • factors
  • concentration of reactants (initial determinant)
  • catalyst
  • pH, pressure, temperature

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  • Chemical Equilibrium is reached when the rates
    of
  • forward and reverse reactions are equal.
  • Equilibrium constant is the ratio of products to
    reactants
  • A catalyst can increase the rate of reaction.

A B X Y Keq X
Y A B
56
  • pH Concentration of positively charged (H) ions
  • dissociation products of H2O (H, OH-) are
    constantly liberated
  • when H is produced, it combines with a H2O
    molecule (hydronium ion - H3O)
  • dissociation of water is a reversible rxn
  • H2O H OH-

_at_ 25o C H OH 10-14 M2 In
pure water H OH 10-7M
57
  • pH -log H log 1
  • H
  • In pure water _at_ 25o C, H 10-7 M
  • pH -log 10-7 7 (Neutral)
  • higher value than 7 is basic
  • lower than 7 is acidic
  • pH is an important property of a biological
    fluid
  • Different cellular organelles have selective pH
  • Maintenance of precise pH is imperative for
    cellular function
  • Change in pH a way of controlling cell activity

58
  • ACIDS and BASES
  • Acid, any molecule that releases H
  • Base, any molecule that combines with H
  • organic molecules are acidic (COOH) produce COO-
  • O O
  • X-COOH X-C X-C H
  • H O
  • X-NH2 H X-NH3
  • - Whenever add acid, increase in H
  • add base, increase in
    OH- or decrease in H
  • - All solutions contain some H and OH
  • Biological molecules can have both acidic and
    basic groups
  • pH determines the degree to which H/OH groups
    are released



-
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  • COO-
  • H - C NH3
  • R

COOH H - C - NH2 _at_ pH 7.0
R Amino acid
Zwitter Ions (neutral) Doubly ionized form
pH
  • COOH
  • H - C NH3
  • R
  • COO-
  • H - C NH2
  • R

pH
60
Molecules have multiple acidic/basic groups HA
H A- Ka
H A- HA log Ka
log H log A- HA pH
pKa log A-
HA pKa is the pH at which 50 of molecules are
dissociated, the other 50 being neutral
(Henderson Hasselbalch Equation)
61
  • pH must be maintained near 7.2 in the cell
    cytoplasm
  • buffers are weak acids or bases
  • (soak up H and OH- ions
  • ability of a buffer to minimize the change in pH
    (buffering capacity)
  • pKa shows the buffering capacity
  • Example is phosphoric acid (3 groups capable of
    dissociating)
  • O
  • H3PO4 HO P OH H2PO4- H pKa
    2.1
  • OH H PO42- H pKa 7.2
  • PO43- H pKa 12.7
  • Physiologically important buffer (cytosol pH 7.2,
    blood 7.4)


62
  • ENERGY defined as the ability to do work
  • Kinetic (the energy of movement)
  • - Heat/thermal Radiant- photons Electric -
    electrons
  • Potential (stored energy)
  • - Chemical bonds Concentration gradient
    Electric potential
  • - Important in biological systems
  • - Glucose is the central molecule
  • The law of thermodynamics
  • - Energy is neither created nor destroyed
  • - converted from one form to another
  • - Unit Calorie (cal) 4.18 Joules
  • 1000 cals 1kcal

63
ATP Adenosine triphosphate (Appp) (the
cellular currency for energy)
O
O
O



Base
O- P- O P- O P O H2C
O-
O-
O-
Sugar
  • Phosphoanhydride bonds
  • (High energy bonds) -7.3 kcal/mole, moderate
  • Package (easy to make, can drive many rxns)
  • Captures and transfers energy
  • used to transfer P to one of the reactants
  • (high energy intermediate)
  • difference in energy released from ATP vs AMP

64
  • WHAT CAN THE ATP BE USED FOR
  • macromolecular synthesis
  • cell movement (muscle contraction)
  • transport molecule in/out cell
  • generate concentration gradients
  • generate electric potential (nerve impulse)

65
  • ENZYMES
  • straining of covalent bonds
  • excitation of e-
  • overcome mutual repulsion of e- cloud
  • In biological systems kinetic energy of
    colliiding
  • molecules is insufficient
  • act primarily by reducing the activation energy
  • facilitate movement of H atoms / e- / protons
  • strain bonds and stabilize transition state
  • formation of covalent bonds
  • Proteins, highly specific substrates
  • catalysts do not change themselves

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